Method for stimulating living body more accurately and apparatus using the same

ABSTRACT

An apparatus for more accurately stimulating a living body comprises: a stimulation unit configured to apply a bio-stimulation signal in vicinity to a living body, the bio-stimulation signal being composed of pieces of time-series data having a specific frequency; and a control unit configured to derive bio-stimulation information required to achieve targeted bio-information using time space data indicative of bio-responses interacting at a plurality of different positions in response to the bio-stimulation signal, and derive a relation between the bio-stimulation signal and the bio-responses, and control the stimulation unit to apply the bio-stimulation signal in response to the derived bio-stimulation information. The relation is configured to set the bio-stimulation information as variables in an X matrix (m, t), set the bio-response information as variables in a Y matrix (n, t), and derive an A matrix (n, m) satisfying Y=AX.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates, in general, to a method of moreaccurately stimulating a living body and an apparatus using the methodand, more particularly, to a method that is capable of more accuratelystimulating a living body by deriving a systematic algorithm betweenbio-related measurement information and stimulation information and toan apparatus using the method.

2. Description of the Related Art

Methods of stimulating a specific portion of a brain are mainlyclassified into invasive stimulation methods and non-invasivestimulation methods.

Generally, such an invasive stimulation method is a method of exactlyinstalling an electrode at a specific target position via surgery,applying an electrical signal to the electrode, and then directlystimulating a specific portion of the brain.

The invasive stimulation method is an accurate and effective stimulationmethod, but has a limitation in that a danger caused by brain surgerymay be present, and thus this method is limitedly used only in the caseof very serious brain diseases, such as Parkinson's disease.

A non-invasive stimulation method is a method of attaching an electrodeto a specific position of the scalp, applying electrical and magneticsignals to the electrode, and stimulating a specific portion of thebrain.

Such a non-invasive stimulation method is limited in that it isdifficult to exactly stimulate the specific portion of the brain, thusrequiring a process of trial and error.

Therefore, the non-invasive stimulation method must include the step ofstimulating a specific position of the scalp for a predetermined periodof time, the step of determining whether the specific position that istargeted is actually stimulated by using a brain signal measurementdevice, such as Electroencephalography (EEG) equipment or a functionalMagnetic Resonance Imaging (fMRI) scanner, and the step of, if it isdetermined that the specific position has not been stimulated, changingthe position of the electrode, stimulating a new specific position ofthe scalp, and determining whether the new position is actuallystimulated by the repositioned electrode.

That is, the non-invasive stimulation method is problematic in that itrequires a process of trial and error, thus repeatedly stimulatinginaccurate positions.

In particular, when such inaccurate positions are repeatedly stimulated,the non-invasive stimulation method may not obtain targeted effects ormay obtain effects lower than the targeted effects, and may cause aproblem in safety because a stimulation time is lengthened.

Such conventional cranial nerve stimulation technology includes U.S.Pat. No. 7,460,903 (entitled “Method and system for a real time adaptivesystem for effecting changes in cognitive-emotive profiles”).

Such a conventional cranial nerve stimulation technology includes thestep of acquiring various bioelectric signals required to determine acurrent psychological state, the step of comparing the currentpsychological state so as to extract a multi-dimensionalcognitive-emotive profile based on the bioelectric signals; mapping thecognitive-emotive profile onto a set of commands; the step of deliveringbrain stimulation commands to drive therapeutic and non-therapeuticstimulus intervention; and the step of applying a prolonged change tothe cognitive-emotive profile.

However, such conventional cranial nerve stimulation technology isproblematic in that it is implemented using a method in which acquiredinformation matches a command set in which output informationcorresponding to input information is preset, thus requiring theabove-described process of trial and error so as to create the presetcommand set.

Further, since the command set used in this way is either createddepending on experience rules or created using the mechanism ofbio-related information that is academically identified, there is alimitation in that the command set is dependent on incomplete experiencerules or limited biological mechanisms, thus causing restrictions inprecision and accuracy.

SUMMARY OF THE INVENTION

Accordingly, the present invention has been made keeping in mind theabove problems occurring in the prior art, and an object of the presentinvention is to provide a method of deriving a systematic algorithmbetween bio-related information and stimulation information, which canmake more accurate and safely stimulation upon applying bio-stimulationbased on acquired bio-related information.

Another object of the present invention is to provide a method forstimulating a living body and an apparatus using the method, which canminimize a process of trial and error using a systematic algorithm.

A further object of the present invention is to provide a method that iscapable of more accurately stimulating a living body by exactlydetermining a specific target stimulation position using a systematicalgorithm, and an apparatus using the method.

In order to accomplish the above objects, the present invention providesa method of more accurately stimulating a living body, includingdetermining targeted bio-information; deriving bio-stimulationinformation required to achieve the targeted bio-information usingcomplicated time space data indicative of bio-responses interacting at aplurality of different positions in response to bio-stimulation composedof pieces of time-series data having a specific frequency; and applyinga stimulation signal to the living body in response to the derivedbio-stimulation information.

Preferably, information about bio-responses to the bio-stimulation maybe a relation between the bio-stimulation and the bio-responseinformation, the relation being analyzed by performing applying thebio-stimulation; and acquiring information about a bio-response to theapplied bio-stimulation.

Preferably, the relation between the bio-stimulation and thebio-response information may be configured to set information about thebio-stimulation as variables in an X matrix (m,t), set the bio-responseinformation as variables in a Y matrix (n,t), derive an A matrix (n,m)satisfying Y=AX, and use the A matrix as the relation between thebio-stimulation and the bio-response information.

Preferably, values in the A matrix may be determined to be mean valuesof values derived during respective repetitions.

Preferably, values in the A matrix may be derived using a pseudo-inversemethod when a plurality of types of bio-stimulation and informationabout a plurality of bio-responses to the bio-stimulation are acquired.

Further, the present invention provides an apparatus for more accuratelystimulating a living body, including a stimulation unit for applying abio-stimulation signal in close vicinity to a living body; and a controlunit for deriving bio-stimulation information required to achievetargeted bio-information using information about a bio-response tobio-stimulation, and controlling the stimulation unit so that thestimulation unit applies the bio-stimulation signal in response to thederived bio-stimulation information.

Preferably, the apparatus may further include an environment sensor foracquiring surrounding environmental information of the living body; anda measurement unit for acquiring bio-related information in closevicinity to the living body, wherein the control unit analyzes arelation between the surrounding environmental information of the livingbody acquired by the environment sensor and the bio-related informationacquired by the measurement unit and uses the relation to derivebio-stimulation information required to achieve the targetedbio-information.

Details of other embodiments are included in the following detaileddescription and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram showing an apparatus for more accuratelystimulating a living body according to an embodiment of the presentinvention;

FIG. 2 is a diagram showing the configuration of a system to which theapparatus for more accurately stimulating a living body is appliedaccording to an embodiment of the present invention;

FIG. 3 is a flowchart showing a method for more accurately stimulating aliving body according to an embodiment of the present invention; and

FIG. 4 is a flowchart showing a method of driving an A matrix accordingto an embodiment of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The above and other objects, features and advantages of the presentinvention will be more clearly understood from the following detaileddescription taken in conjunction with the accompanying drawings.However, the present invention is not limited by the followingembodiments and may be implemented in various forms. The presentembodiments are configured to merely make the disclosure of the presentinvention complete and are provided to fully describe the scope of thepresent invention to those having ordinary knowledge in the art to whichthe present invention pertains, and the present invention is merelydefined by the scope of the accompanying claims. Meanwhile, the termsused in the present specification are intended to describe embodimentsand are not intended to limit the scope of the present invention.

FIG. 1 is a block diagram showing an apparatus for more accuratelystimulating a living body according to an embodiment of the presentinvention. Referring to FIG. 1, the apparatus for more accuratelystimulating a living body according to the embodiment of the presentinvention includes a stimulation unit 110 for applying a bio-stimulationsignal in close vicinity to a living body, and a control unit 120 forderiving bio-stimulation information required to achieve targetedbio-information and controlling the stimulation unit 110 so that itapplies the bio-stimulation signal in response to the derivedbio-stimulation information.

The stimulation unit 110 applies a bio-stimulation signal capable ofcausing a bio-response in close vicinity to the living body.

For example, the stimulation unit 110 may use electrical stimulation,magnetic stimulation, photic stimulation, ultrasonic stimulation, etc.

Electrical stimulation may be provided using a scheme for applyingDirect Current (DC) stimulation, pulse stimulation, Alternating Current(AC) stimulation, or random noise stimulation through an electrodeinstalled in close vicinity to a living body. Magnetic stimulation mayenable a magnetic stimulus to be applied using a coil for generating amagnetic field in close vicinity to a living body. Further, photicstimulation may enable a stimulus to be applied by emitting infraredrays, near-infrared rays, visible rays, or laser light to a living body.Furthermore, ultrasonic stimulation may enable a stimulus to be appliedvia an ultrasonic transducer or an ultrasound transceiver, which createsan ultrasonic vibration when in contact with the living body.

Preferably, the stimulation unit 110 applies stimulation to the brainamong portions of the living body, and may use transcranial directcurrent stimulation (tDCS), transcranial alternating current stimulation(tACS), transcranial pulsed current stimulation (tPCS), etc.

Further, preferably, the stimulation unit 110 may be configured to beincluded in a portable headset worn on the head and may be designed toeasily apply stimulation to the brain among the portions of the livingbody.

The apparatus for more accurately stimulating the living body accordingto the embodiment of the present invention further includes ameasurement unit 130 for acquiring bio-related information in closevicinity to the living body.

Preferably, the measurement unit 130 measures the activities of thebrain using brain waves, a brain evoked potential, brain activity,magnetoencephalogram, ultrasonic waves, etc.

For example, the measurement unit 130 may be implemented using anElectroencephalogram (EEG) sensor, a near infrared spectrophotometer (ornear infrared spectroscopy: NIRS), magnetoencephalography (MEG)equipment, an ultrasound transceiver, or the like.

In an example, the measurement unit 130 is implemented as an electrodeattached to the scalp and is capable of measuring the electricalactivities of the brain, and the brain wave measurement electrode may beimplemented using a capacitive electrode which has conductivity, but hasa surface coated with a nonconductive material.

Further, the brain wave measurement electrode may preferably be used ina non-contact manner.

In another example, the measurement unit 130 is implemented as anelectrode attached to the scalp and is capable of measuring the magneticactivities of the brain.

In a further example, the measurement unit 130 may measure a brainevoked potential. The brain evoked potential refers to theelectrophysiological response of the brain to stimulation, and any ofsensible, cognitive, and motional stimuli may be applied as suchstimulation.

As detailed examples, the measurement unit 130 may measure EEG from abody to which electrical, magnetic, photic, or ultrasonic stimulation isapplied, and may determine the measured EEG to be the brain evokedpotential.

In yet another example, the measurement unit 130 may acquire brainactivity using a near infrared spectrophotometer (or NIRS) that exploitsa light source for radiating light having a specific wavelength, such asnear infrared rays, and a light receiving device (photodetector) foranalyzing light absorption caused by the activities of the brain.

In this case, the measurement unit 130 may include a plurality of lightsources and photodetectors so as to detect the activation of the braindepending on positions at the brain.

In still another example, the measurement unit 130 may be implementedusing an ultrasonic coupler and an ultrasonic receiver, or an ultrasoundtransceiver which is a combination thereof, and may measure thestructure of the brain and the activities of blood vessels.

Preferably, the measurement unit 130 may be configured to acquirebio-information using a plurality of electrical, magnetic, photic, orultrasonic components. According to the configuration of the measurementunit 130, the stimulation unit 110 may be configured to applybio-stimulation using the plurality of electrical, magnetic, photic, orultrasonic components.

The control unit 120 derives bio-stimulation information required toachieve targeted bio-information using information about a bio-responseto bio-stimulation, and controls the stimulation unit 110 so that itapplies a bio-stimulation signal in response to the derivedbio-stimulation information.

In accordance with a preferred embodiment of the present invention, thecontrol unit 120 repeatedly performs a procedure for applyingbio-stimulation and acquiring information about a bio-response to theapplied bio-stimulation, derives a relation between the bio-stimulationand the bio-response information, and uses the relation as theinformation about the bio-response to the bio-stimulation.

In accordance with another preferred embodiment of the presentinvention, the control unit 120 sets information about bio-stimulationas variables in an X matrix (m,t), sets information about thebio-response to the bio-stimulation as variables in a Y matrix (n,t),derives an A matrix (n,m) satisfying Y=AX, and uses the derived A matrixas information about the bio-response to the bio-stimulation.

Preferably, m may be the type of stimulation (where identicalstimulation at different positions may be regarded as separate stimuli),n may be the type of bio-information (where identical bio-information atdifferent positions may be regarded as pieces of separatebio-information), and t may be the number of repetitions (or the numberof stimulation values and bio-information values acquired for apredetermined period of time).

That is, the control unit 120 sets the targeted bio-information as a Ymatrix using the derived A matrix, derives an X matrix satisfying Y=AX,and determines bio-stimulation information corresponding to a requiredtype (or a required position) according to the X matrix.

In accordance with the preferred embodiment of the present invention,values in the A matrix are determined to be mean values of valuesderived during respective repetitions.

Preferably, values in the A matrix are determined in such a way as tolimit the type of stimulation (for example, a value is applied only tosingle stimulation and the remaining values are set to ‘0’), acquire abase vector of the A matrix using the acquired bio-information, anddetermine the values in the A matrix to be mean values of values of basevectors obtained by repeating a base vector acquisition procedure.

In accordance with another embodiment of the present invention, valuesin the A matrix may be obtained using a pseudo-inverse method.

For example, when a plurality of stimulation values and a plurality ofbio-information values are repeatedly acquired, a pseudo-inverse matrixmay be configured and thereafter values in the A matrix may be obtained.

When there are a number of equations more than a number of unknownvalues, a method using the pseudo-inverse matrix is used to obtain aleast squares solution, and this method may be usefully applied to thepresent invention.

In the simplest example, a method using a pseudo-inverse matrix is usedto obtain the least squares solution when the number of pieces ofinformation about values to be obtained from a quadratic equation isgreater than two pairs and then a solution cannot be obtained.

For example, such a method is configured to, if it is assumed that Amatrix [a, b] is obtained for X matrix

$\begin{bmatrix}x \\1\end{bmatrix}\quad$and for Y matrix [y], obtain a and b values required to minimize errorwhen assuming that values of x are (x₁, x₂, . . . , x_(i)) and values ofy corresponding thereto are (y₁, y₂, . . . , y_(i)).

In an example of the method applied to the present invention, thecontrol unit 120 changes variables in the X matrix as bio-stimulationhas changed, and changes variables in the Y matrix as bio-informationwhich is the bio-response to the bio-stimulation has changed, and then aplurality of equations Y=AX are derived. In this case, there may occur acase where the control unit 120 cannot determine the solution of the Amatrix to be a single solution due to measurement noise or the like. Inthis case, the A matrix for minimizing error may be obtained using thepseudo-inverse matrix.

The method using the pseudo-inverse matrix is advantageous in that, evenwhen relations between stimulation values and bio-information values areunclear due to noise or the like, the A matrix for minimizing error maybe derived.

More preferably, the control unit 120 may derive and use the A matrix byperforming repetitive stimulation and measurement on a single livingbody via the stimulation unit 110 and the measurement unit 130.

Further, the control unit 120 may derive bio-stimulation informationrequired to achieve targeted bio-information, based on the A matrixderived via stimulation and measurement performed on a plurality ofliving bodies.

Although, in the above description, for the convenience of description,an object for deriving the A matrix is described as being the apparatusof the present invention to be claimed, the A matrix is not necessarilycalculated by the apparatus including both the measurement unit and thestimulation unit, and a case where the A matrix obtained according tothe above description is obtained from the outside of the apparatus andis then used may also be included in the scope of the present invention.

The apparatus for more accurately stimulating a living body according toanother preferred embodiment of the present invention further includesan environment sensor 140 for acquiring the surrounding environmentalinformation of a living body.

In this case, the control unit 120 analyzes a relation between thesurrounding environmental information of the living body acquired by theenvironment sensor 140 and bio-related information acquired by themeasurement unit 110, similarly to a manner in which the relationbetween the stimulation information and the bio-response information isderived.

Preferably, the surrounding environmental information of the living bodyacquired by the environment sensor 140 may be used as variables in the Xmatrix upon deriving the A matrix. Preferably, the environment sensor140 is a device for measuring temperature, humidity, illuminance, noise,or the like in surrounding environment that may influence bio-signals.

The apparatus for more accurately stimulating a living body according toa further embodiment of the present invention may be configured totransmit acquired information to a platform database (DB) 150 via acommunication terminal or its own communication unit.

The platform DB 150 stores the bio-response information, thebio-stimulation information, and the A matrix which is a relationbetween the bio-response information and the bio-stimulationinformation, as complicated space-time data.

Preferably, the platform DB 150 stores the bio-response information asfrequency variation information over time using a wavelet transform.

Preferably, the platform DB 150 additionally stores analysis resultsderived using phase synchrony, partial directed coherence (PDC) orgranger causality analysis methods.

Further, the platform DB 150 preferably stores surrounding environmentalnoise and environmental information measured by a gyroscope and anaccelerometer, with the noise and the environmental informationtime-locked to the bio-response information, the bio-stimulationinformation, and the A matrix which is the relation between the twotypes of information.

The platform DB 150 may individually map such various types ofinformation to a multi-dimensional space, and store the various types ofinformation so that they may be classified for respective features.

The platform DB 150 has big data storage characteristics, and may havethe form of a distributed DB with high update performance, such as aCassandra DB, or the form of a distributed file system (DFS) with highprocessing throughput, such as a Hadoop DB. Alternatively, the platformDB 150 may have both the two forms.

FIG. 2 is a diagram showing the configuration of a system to which theapparatus for more accurately stimulating a living body is appliedaccording to an embodiment of the present invention. Referring to FIG.2, the system includes the apparatus for more accurately stimulating aliving body according to the embodiment of the present invention or aterminal 210 for receiving information from the apparatus, a server 220for receiving data from the apparatus or the terminal 210 and processingthe data, a DB 230 for receiving the data from the server 220 andprocessing or storing the data, and a second user terminal 240 forrequesting data from the server 220.

As described above with reference to FIG. 1, the apparatus or theterminal 210 has bio-stimulation information and bio-responseinformation, and transmits the information to the server 220 through asignal processing unit.

Preferably, the apparatus or the terminal 210 transmits not onlybio-stimulation information and bio-response information, but also Amatrix data, signal-processed metadata, the location of the apparatus orthe terminal, personal information, etc. using various communicationmethods.

The server 220 transforms or processes the information received from theapparatus or the terminal 210 into a data format that can be processedby the server by performing information processing on the receivedinformation based on a preset event-action rule.

The server 220 stores the transformed or processed data in the DB 230.

Preferably, the DB 230 includes a primary DB 231 with a high updatespeed (for example, the above-described distributed DB [a detailedexample: a Cassandra DB]) and a secondary DB 232 having high semanticinformation extraction performance (for example, the above-described DFS[a detailed example: a Hadoop DB]).

The secondary DB 232 extracts semantic information from the stored DBaccording to a preset statistical or algorithmic scheme, and stores orprocesses the extracted semantic information.

The primary DB 231 and the secondary DB 232 may be integrated into asingle DB.

The server 220 stores the transformed or processed data in the primaryDB 231, and stores some data, which can be stored or deleted or whichenables semantic information thereof to be processed according to thetype and format of data, in the secondary DB 232.

The server 220 may extract data from the DB 230 and provide theextracted data when the second user terminal 240 requests data.

Preferably, the server 220 may be configured to permit only the accessof the second user terminal 240, the apparatus or the terminal 210,which conforms to a program corresponding to a preset scheme (forexample, Software Development Kit: SDK or Application ProgrammingInterface: API), with respect to respective attempts to access.

FIG. 3 is a flowchart showing a method of more accurately stimulating aliving body according to an embodiment of the present invention. Aprocedure for performing individual steps shown in FIG. 3 is apparentaccording to the description made with reference to FIGS. 1 and 2, andthus a detailed description thereof will be omitted.

Referring to FIG. 3, in the method for of more accurately stimulating aliving body according to the embodiment of the present invention, thestimulation apparatus performs the step S310 of acquiring an A matrixand the step S320 of determining targeted bio-information.

The stimulation apparatus may first determine targeted bio-informationor may first acquire the A matrix. However, the A matrix must beacquired before bio-stimulation information is derived.

The step S310 of acquiring the A matrix may be configured such that thestimulation apparatus acquires the A matrix by repeating the applicationof stimulation and measurement of response information, or derives the Amatrix by acquiring information from the outside, or acquires the Amatrix by receiving a completed A matrix.

In accordance with a preferred embodiment of the present invention, thestimulation apparatus may perform the step S330 of acquiring surroundingenvironmental information, and the step S340 of acquiring bio-relatedinformation under the condition of the acquired surroundingenvironmental information. These steps are required to perform the Amatrix change step S350 of further advancing the A matrix, wherein, inthis case, the stimulation apparatus must perform the A matrixacquisition step S340 before the A matrix change step S350 is performed.

Thereafter, since the stimulation apparatus acquires the targetedbio-information and the A matrix as information, it performs the stepS360 of deriving bio-stimulation information required to achievetargeted bio-information, based on the information, and the step S370 ofstimulating the living body based on the derived bio-stimulationinformation.

Further, the stimulation apparatus according to a predeterminedembodiment of the present invention may perform the step S380 oftransmitting the acquired information to the server, and suchinformation transmission may be performed at any step.

FIG. 4 is a flowchart showing a method of deriving an A matrix accordingto an embodiment of the present invention. The procedure for performingindividual steps shown in FIG. 4 is apparent by the description madewith reference to FIG. 1, and thus a detailed description thereof willbe omitted.

Referring to FIG. 4, in the method of deriving an A matrix according tothe embodiment of the present invention, an analysis device for derivingan A matrix may sequentially perform the step S410 of stimulating aliving body, the step S420 of acquiring information about a bio-responseto such stimulation, and the step S440 of deriving an A matrix which isa relation between the bio-stimulation and the bio-response.

Preferably, the analysis device may further perform the step S430 ofdetermining whether a predetermined number of pieces of information havebeen acquired so as to repeat the step S410 of stimulating the livingbody and the step S420 of acquiring bio-response information until apredetermined number of pieces of information are accumulated.

Further, preferably, the analysis device may transmit the derived Amatrix to the server.

As described above, the present invention is advantageous in that itderives a systematic algorithm between bio-related information andstimulation information, which can make more accurate and safelystimulation upon applying bio-stimulation based on acquired bio-relatedinformation.

Further, the present invention is advantageous in that it can minimize aprocess of trial and error using a systematic algorithm.

Furthermore, the present invention is advantageous in that it can moreaccurately stimulate a living body by exactly determining a specifictarget stimulation position.

Although the preferred embodiments and applied embodiments of thepresent invention have been illustrated and described, those skilled inthe art will appreciate that the present invention is not limited by theabove-described specific embodiments and applied embodiments and variousmodifications are possible, without departing from the scope and spiritof the invention as disclosed in the accompanying claims. Thesemodifications should not be understood separately from the technicalspirit or prospect of the present invention.

What is claimed is:
 1. An apparatus for more accurately stimulating aliving body, comprising: a stimulation unit configured to apply abio-stimulation signal in vicinity to a living body, the bio-stimulationsignal being composed of pieces of time-series data having a specificfrequency; and a control unit configured to derive bio-stimulationinformation required to achieve targeted bio-information using timespace data indicative of bio-responses interacting at a plurality ofdifferent positions in response to the bio-stimulation signal, andderive a relation between the bio-stimulation signal and thebio-responses, and control the stimulation unit to apply thebio-stimulation signal in response to the derived bio-stimulationinformation, wherein the relation is configured to set thebio-stimulation information as variables in an X matrix (m, t), set thebio-response information as variables in a Y matrix (n, t), and derivean A matrix (n, m) satisfying Y=AX.
 2. The apparatus of claim 1, furthercomprising: an environment sensor configured to acquire surroundingenvironmental information of the living body; and a measurement unitconfigured to acquire bio-related information in vicinity to the livingbody, wherein the control unit is configured to analyze a relationbetween the surrounding environmental information of the living bodyacquired by the environment sensor and the bio-related informationacquired by the measurement unit and use the relation to derive thebio-stimulation information required to achieve the targetedbio-information.
 3. The apparatus of claim 1, wherein values in the Amatrix are determined to be mean values of values derived duringrespective repetitions.
 4. The apparatus of claim 1, wherein values inthe A matrix are derived using a pseudo-inverse method to obtain theleast squares solution when a plurality of types of bio-stimulation andinformation about a plurality of bio-responses to the bio-stimulationare acquired.